1916
Stereochemistry of Sulfur Compounds. V. Stereochemical Reaction Cycles That Involve Cyclic Sulfoxides, Sulfimides, and Sulfoximides' Frederick G . Yamagishi, Dennis R. Rayner, Evelyn T. Zwicker,2 and Donald J. Cram*
Contribution f r o m the Department of Chemistry, Unioersity of California at Los Angeles, Los Angeles, California 90024. Received August 12, 1972 Abstract: A new scheme is reported for the preparation of optically pure sulfoxides, sulfoximides, and sulfimides and is applied to cyclic sulfur compounds otherwise unavailable in optically active form. Racemic 2,3-dihydro1-oxide (4a) with hydrazoic benzo[b]thiophene 1-oxide (la) was converted to 2,3-dihydrobenzo[h]thiophene-l-imide acid. Fractional crystallization of its diastereomeric N-d-10-camphorsulfonyl derivatives gave one optically pure isomer, hydrolysis of which gave (+)-4a of maximum rotation. Treatment O f (+)-4a with nitrosyl hexafluorophosphate gave (-)-1 of maximum rotation which with either N-sulfinyl-p-toluenesulfonamideor N,N'-bis(p-toluene( -)-2a. sulfony1)sulfur diimide in pyridine gave ( -)-N-p-toluenesulfonyl-2,3-di~ydrobenzo[b]thiophene-l-imide, Although attempted base-catalyzed hydrolysis of ( -)-2a gave only benzo[b]thiophene, sulfuric acid catalyzed hydrolysis of (-)-2a of maximum rotation gave (-)-la of 26z maximum rotation. Oxidation of (-)-2a with potassium permanganate, nitrenation of (-)-la with tosyl azide and copper, or sulfonation of (+)-4a with tosyl chloride in pyridine all gave (-)-3a of maximum rotation except the nitrenation, which was 77 stereospecific. (-)-3a is retention of configuration. Similar reactions The stereochemical course of transformation (+)-4a were carried out with 5-bromo-2,3-dihydrobenzo[~]thiophene 1-oxide (lb). Analogies and mechanistic considerations strongly imply that the following three reactions in both the a and b series take the same stereochemical course (-)-1; (-)-1 + (-)-3; (-)-2 (-)-3. From the symmetry properties of the five (retention): (+)-4 (-)-2 occurs stereochemical reaction cycles implicit in the above transformations, it is concluded that (-)-1 --, in pyridine with inversion of configuration in both the a and b series of compounds. Similarities between optical (6) of known absolute rotatory dispersion curves of 2a, 2b, and N-p-toluenesulfonyl-S-methyl-S-p-tolylsulfimide configuration provided a basis for making tentative assignments of absolute configuration to all of the cyclic compounds. In benzene without pyridine, ( + ) - l b with N,N-bis(p-toluenesulfony1)sulfurdiimide gave (-)-2b, the reaction going with 95 retention of configuration. Similarly in benzene without pyridine, (+)-methyl p-tolyl sulfoxide ($1-5 gave (i-1-6 with 94% net retention. Unlike the reaction (+)-5 (-)4 in pyridine that is second ( + ) - 6 in benzene is close to first order in the sulfur diimide. The conversions order in the sulfur diimide, (+)-5 of sulfoxide to sulfimide in both pyridine and benzene are 50 to 100 times faster in the cyclic compared to the open-chain system. The mechanisms are discussed. -f
-f
-f
-
-f
An
earlier paper3&described a series of stereochemical reaction that involved interconversions of open-chain sulfoxide, sulfimide, and sulfoximide. Both nucleophilic and electrophilic substitution reactions at chiral sulfur were involved. This paper reports a similar study of the stereochemical course of interconversions of the same classes of compounds based on the 2,3-dihydrobenzo[b]thiophene and 5 bromo-2,3-dihydrobenzo[b]thiophene ring systems. Of particular interest was the effect of the constraints of the five-membered ring system on the stereochemical course and rate of the conversions of sulfoxides 1 to
-xw
XQQ
oy
./-
\..
la, X = H
b, X = Br
2a, X =
NTs
H
b,X=Br
sulfimides 2. To make the study, a new method of obtaining optically pure sulfoxides and their deriva( I ) This investigation was supported by U. S . Public Health Service Research Grant No. G M 12640-05 from the Department of Health, Education and Welfare. (2) National Science Foundation Summer Undergraduate Research Participant, 1971, (3) (a) D. J. Cram, J. Day, D. R. Rayner, D. M. von Schriltz, D. J. Duchamp, and D. C. Garwood, J . Amer. Chem. SOC.,9 2 , 7369 (1970); (b) D. C. Garwood and D. J. Cram, ibid., 92, 4575 (1970).
Journal of the American Chemical Society
1
95:6
tives had to be developed. An additional point of interest was illustration of the use of stereochemical reaction cycles as an aid to correlations of configurations and determinations of the steric courses of substitution reactions at chiral centers. Sb
Results Syntheses. Reduction of 2,3-dihydrobenzo[b]thiophene 1, I-dioxide4" with lithium aluminum hydride gave 2,3-dihydroben~o[b]thiophene~~ (75 %), which with SOdium metaperiodate gave racemic 2,3-dihydrobenzo[blthiophene 1-oxide5 (la) (10Oz). This material was converted with hydrazoic acid6 to 2,3-dihydrobenzo[b]thiophene-1-imide 1-oxide (4a, 75 %). Reaction of 4a with (+)-d-10-camphorsulfonyl chloride in pyridine gave a crystalline mixture of diastereomers, the less soluble of which was crystallized to purity (22% ~ v e r a l l ) . ~Treatment of this material with con(4) (a) F. G. Bordwell and W. H. McICellin, J. Amer. Chew. Soc., 72, 1985 (1950); (b) S . F. Birch, J . Inst, Petrol., London, 39, 185 (I953), reported only the preparation and boiling point of this compound. ( 5 ) S . F. Birch, R. A . Dean, and E. V. Whitehead, J . I n s t . Pefrol., London, 40, 76 (1954). (6) F. Misiani, T. W. Fair, and L. Reiner, J . A m e r . Chem. Soc., 73, 459 (1951). (7) Diastereomeric N-sulfonylsulfoximides have been previously prepared and separated by crystallization : M. Barash, Nature (LOndO17), 187, 591 (1960). Sulfoximides have been resolved through salt formation with optically active sulfonic acids: R. Fusco and F. Tenconi, Chim. Ind. (Milan), 47, 61 (1965). Racemic 4a did not form a crystalline salt with d-10-camphorsulfonic acid in our hands.
March 21, 1973
1917
centrated sulfuric acid produced sulfoximide (+)4a (64Z). This material was converted t o sulfoxide (-)-la' with nitrosyl hexafluorophosphate in nitromethane3" (91 %), which was identical in its infrared and nmr spectrum with those of (*)-la used as the primary starting material for the sequence. With either N-sulfinyl-p-toluenesulfonamides or N , N ' bis(ptoluenesulfony1)sulfur diimide (DIM) in pyridine, sulfoxide (-)-la gave sulfimide (-)-2a of essentially maximum rotation in 50 and 78% yields, respectively. Hydrolysis of sulfimide (-)-2 with concentrated sulfuric acid at 25" gave back sulfoxide ( - ) - l a of 26 2 optical purity and in 74% yield. All attempts t o hydrolyze (-)-2a to ( - ) - l a with base gave benzo[b]thiophene essentially quantitatively. Oxidation of sulfimide (-)-2a with potassium permanganate in pyridine-water gave 31 % sulfoximide (-)-3a of essentially maximum rotation. Nitrenation of sulfoxide ( - ) - l a with tosyl azide and copperg gave 24 % sulfoximide (-)-3a of 77% optical purity. Sulfoximide (+)-4a was treated with tosyl chloride in pyridine to give (-)-3a of maximum rotation in 84 yield. Bromination'O of 2,3-dihydrobenzo[b]thiophene in acetic acid gave 5-bromo-2,3-dihydrobenzo[b]thiophene (97 %). The position of bromination resembles that observed for 2-methylphenylmercaptoacetic acid under the same conditions. lo Also, . 6-bromo-2,3-dihydrobenzo[b]thiophene 1,l-dioxide" possesses mp 141142", whereas our dioxide gave mp 131.5-132.5". Compound 4b was prepared and resolved as was 4a, and the interconversions of optically active 4b, l b , 2b, and 3b were stereochemically similar to those of the a series, and in general, the yields were higher. For example, deimidation of (-)-4b with nitrous acidL2 gave ( + ) - l b essentially quantitatively and with complete retention of configuration. Nitrous acid is superior t o nitrosyl hexafluorophosphate for the deimidation. These series of reactions provide a new way of obtaining optically active sulfoxides, sulfimides, and sulfoximides. Chart 1 outlines the interconversions of these compounds. In the b series of compounds, enantiomers of the compounds actually used are formulated. Stereochemical Course of Conversion of Sulfoxides to Sulfimides. Kresze* and coworkers reported the formation of sulfimide from N-sulfinyl-p-toluenesulfonamide l 3 or N,N'-bis(p-toluenesuIfony1)sulfur diimide (DIM) and sulfoxides. We found that pyridine catalyzed these reactions, and in pyridine as solvent at 0", the reactions occurred with essentially complete inversion of configuration. When run in dichloromethane with a catalytic amount of pyridine at 25", 44% net inversion was found. 3a Othersljb observed that 2-(S),S(S)methionine sulfoxide with N-sulfinyl-p-toluenesulfona(8) (a) G. Schultz and G . Kresze, Angew. Chem., Int. Ed. EngI., 75, 1022 (1963); 1671 (1966).
(b) W. Wucherpfennig and G. Kresze, Tetrahedrori Lett.,
(9) H. Kwart and I
